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Titolo:
Human and mouse IFN-beta gene therapy exhibits different anti-tumor mechanisms in mouse models
Autore:
Qin, XQ; Beckham, C; Brown, JL; Lukashev, M; Barsoum, J;
Indirizzi:
Biogen Inc, Cambridge, MA 02142 USA Biogen Inc Cambridge MA USA 02142Biogen Inc, Cambridge, MA 02142 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 4, anno: 2001,
pagine: 356 - 364
SICI:
1525-0016(200110)4:4<356:HAMIGT>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBROBLAST GROWTH-FACTOR; HUMAN INTERFERON-BETA; I INTERFERON; CELL-LINES; CAUSES REGRESSION; ALPHA; MURINE; TUMORIGENICITY; MICE; EXPRESSION;
Keywords:
IFN-beta gene delivery; tumor regression; mouse tumor model; anti-proliferative effect; immune stimulation; NK cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Qin, XQ Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA Biogen Inc 14 Cambridge Ctr Cambridge MA USA 02142 e, MA 02142 USA
Citazione:
X.Q. Qin et al., "Human and mouse IFN-beta gene therapy exhibits different anti-tumor mechanisms in mouse models", MOL THER, 4(4), 2001, pp. 356-364

Abstract

Previously, we suggested that local human interferon-beta (IFN-beta) gene therapy with replication-defective adenoviral vectors can be an effective cancer treatment. Clinical trials to treat cancers with adenovirus expressing the human IFN-beta gene (IFNB1) has been planned. As a continued effort to explore the mechanisms of action of human IFN-beta gene therapy that can occur in the clinical setting, we tested mouse IFN-beta gene therapy in human xenograft tumors in both ex vivo and in vivo models. Delivery of the mouse IFN-beta gene (Ifnb) caused tumor inhibition; this effect was dependent on the indirect anti-tumor activities of IFN-beta, notably a stimulation ofnatural killer cells. IFN-beta does not show cross-species activity in itsanti-proliferative effect and mouse IFN-beta does not cause as significantan anti-proliferative effect on mouse tumor cells as human IFN-beta causeson human tumor cells. Therefore, we believe that mouse models using eitherhuman IFN-beta or mouse IFN-beta gene transfer do not capture all aspects of the action of adenovirus-mediated human IFN-beta gene therapy that may be present in the clinical setting. Due to its multiple mechanisms of action, human IFN-beta gene therapy may be effective in treating human cancers that are either sensitive or resistant to the direct anti-proliferative effect of IFN-beta.

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Documento generato il 28/03/20 alle ore 23:29:05